1-182657603-C-A

Position:

• chr1-182657603-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102450.3(RGS8):​c.193+8366G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.687 in 151,642 control chromosomes in the GnomAD database, including 36,340 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36340 hom., cov: 29)
• Consequence: RGS8 NM_001102450.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.974

Genes affected

RGS8 (HGNC:16810): (regulator of G protein signaling 8) This gene is a member of the regulator of G protein signaling (RGS) family and encodes a protein with a single RGS domain. Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. They accelerate transit through the cycle of GTP binding and hydrolysis to GDP, thereby terminating signal transduction, but paradoxically, also accelerate receptor-stimulated activation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RGS8	NM_001102450.3	c.193+8366G>T		intron_variant		ENST00000515211.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RGS8	ENST00000515211.2	c.193+8366G>T		intron_variant		4	NM_001102450.3	P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104198 AN: 151522 Hom.: 36336 Cov.: 29

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.609

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.669

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.687 AC: 104233 AN: 151642 Hom.: 36340 Cov.: 29 AF XY: 0.687 AC XY: 50879 AN XY: 74092

Gnomad4 AFR AF: 0.581

Gnomad4 AMR AF: 0.655

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.730

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.751

Gnomad4 OTH AF: 0.670

Alfa AF: 0.733 Hom.: 80538

Bravo AF: 0.668

Asia WGS AF: 0.700 AC: 2433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4652741; hg19: chr1-182626738;